当前位置: X-MOL 学术Oncol. Rep. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Hydrostatic pressure stabilizes HIF‑1α expression in cancer cells to protect against oxidative damage during metastasis.
Oncology Reports ( IF 3.8 ) Pub Date : 2021-08-09 , DOI: 10.3892/or.2021.8162
Da Zhai 1 , Yong Xu 2 , Lina Abdelghany 1 , Xu Zhang 1 , Jingyan Liang 3 , Shuohua Zhang 4 , Changying Guo 5 , Tao-Sheng Li 1
Affiliation  

The tissue microenvironment is known to play a pivotal role in cancer metastasis. Interstitial fluid hydrostatic pressure generally increases along with the rapid growth of malignant tumors. The aim of the present study was to investigate the role and relevant mechanism of elevated hydrostatic pressure in promoting the metastasis of cancer cells. Using a commercial device, Lewis lung cancer (LLC) cells were exposed to 50 mmHg hydrostatic pressure (HP) for 24 h. The survival time and morphology of the cells did not notably change; however, the results from a PCR array revealed the upregulation of numerous metastasis‑promoting genes (Hgf, Cdh11 and Ephb2) and the downregulation of metastasis suppressing genes (Kiss1, Syk and Htatip2). In addition, compared with that in the control, the cells which had undergone exposure to 50 mmHg HP showed significantly higher protein expression level of HIF‑1α and the antioxidant enzymes, SOD1 and SOD2, as well as improved tolerance to oxidative stress (P<0.05 vs. control). Following an intravenous injection of the LLC cells into healthy mice, to induce lung metastasis, it was found that the exposure of the LLC cells to 50 mmHg HP for 24 h, prior to injection into the mice, resulted in higher cell survival/retention in the lungs 24 h later and also resulted in more metastatic tumor lesions 4 weeks later (P<0.05 vs. control). Further investigation is required to confirm the molecular mechanism; however, the results from the present study suggested that elevated interstitial fluid HP in malignant tumors may promote the metastasis of cancer cells by stabilizing HIF‑1α expression to defend against oxidative damage.

中文翻译:

静水压力稳定癌细胞中的 HIF-1α 表达,以防止转移过程中的氧化损伤。

已知组织微环境在癌症转移中起关键作用。间质液静水压一般随着恶性肿瘤的快速生长而升高。本研究旨在探讨静水压升高在促进癌细胞转移中的作用及相关机制。使用商业设备,路易斯肺癌 (LLC) 细胞暴露于 50 毫米汞柱静水压力 (HP) 24 小时。细胞的存活时间和形态没有明显变化;然而,PCR阵列的结果揭示了许多促进转移基因(Hgf、Cdh11Ephb2)的上调和转移抑制基因(Kiss1、SykHtatip2)的下调)。此外,与对照组相比,暴露于50 mmHg HP的细胞显示出HIF-1α和抗氧化酶SOD1和SOD2的蛋白表达水平显着升高,并且对氧化应激的耐受性提高(P< 0.05 与对照)。在将 LLC 细胞静脉注射到健康小鼠体内后,为了诱导肺转移,发现在注射到小鼠体内之前,将 LLC 细胞暴露于 50 mmHg HP 24 小时,导致更高的细胞存活/保留24 小时后肺转移,4 周后也导致更多转移性肿瘤病变(与对照相比 P <0.05)。需要进一步研究以确认分子机制;然而,
更新日期:2021-08-09
down
wechat
bug